(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.) > cellular organisms: NE > Bacteria: NE > Proteobacteria: NE > Alphaproteobacteria: NE > Sphingomonadales: NE > Sphingomonadaceae: NE > Novosphingobium: NE > Novosphingobium capsulatum: NE
Warning: This entry is a compilation of different species or line or strain with more than 90% amino acide identity. You can retrieve all strain data
(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.) Novosphingobium capsulatum: N, E.
Molecular evidence
Database
No mutation 1 structure: 1YR2: Prolyl endopeptidase from Sphingomonas capsulata open configuration No kinetic
LegendThis sequence has been compared to family alignement (MSA) red => minority aminoacid blue => majority aminoacid color intensity => conservation rate title => sequence position(MSA position)aminoacid rate Catalytic site Catalytic site in the MSA MKNRLWLAMAAPLALATPVAFAQTPPTLAKDQAMPSLPPYPASPQVPLVE DHFGEKVSDPWRWLEADVRTDAKVAAWVQAQSAYTAAYLKQLPERAALEK RMKALIDYERFGLPQRRGASVFYSWNSGLMNQSQLLVRPADAPVGTKGRV LLDPNTWAKDGATALDAWAASDDGRLLAYSVQDGGSDWRTVKFVGVADGK PLADELKWVKFSGLAWLGNDALLYSRFAEPKEGQAFQALNYNQTVWLHRL GTPQSADQPVFATPELPKRGHGASVSSDGRWVVITSSEGTDPVNTVHVAR VTNGKIGPVTALIPDLKAQWDFVDGVGDQLWFVSGDGAPLKKIVRVDLSG STPRFDTVVPESKDNLESVGIAGNRLFASYIHDAKSQVLAFDLDGKPAGA VSLPGIGSASGLSGRPGDRHAYLSFSSFTQPATVLALDPATAKTTPWEPV HLTFDPADFRVEQVFYPSKDGTKVPMFIVRRKDAKGPLPTLLYGYGGFNV ALTPWFSAGFMTWIDSGGAFALANLRGGGEYGDAWHDAGRRDKKQNVFDD FIAAGEWLIANGVTPRHGLAIEGGSNGGLLIGAVTNQRPDLFAAASPAVG VMDMLRFDQFTAGRYWVDDYGYPEKEADWRVLRRYSPYHNVRSGVDYPAI LVTTADTDDRVVPGHSLKYTAALQTAAIGPKPHLIRIETRAGHGSGKPID KQIEETADVQAFLAHFTGLTPRP
References
Title: Structural and mechanistic analysis of two prolyl endopeptidases: role of interdomain dynamics in catalysis and specificity Shan L, Mathews, II, Khosla C Ref: Proc Natl Acad Sci U S A, 102:3599, 2005 : PubMed
Prolyl endopeptidases (PEPs) are a unique class of serine proteases with considerable therapeutic potential for the treatment of celiac sprue. The crystal structures of two didomain PEPs have been solved in alternative configurations, thereby providing insights into the mode of action of these enzymes. The structure of the Sphingomonas capsulata PEP, solved and refined to 1.8-A resolution, revealed an open configuration of the active site. In contrast, the inhibitor-bound PEP from Myxococcus xanthus was crystallized (1.5-A resolution) in a closed form. Comparative analysis of the two structures highlights a critical role for the domain interface in regulating interdomain dynamics and substrate specificity. Structure-based mutagenesis of the M. xanthus PEP confirms an important role for several interfacial residues. A salt bridge between Arg-572 and Asp-196/Glu-197 appears to act as a latch for opening or closing the didomain enzyme, and Arg-572 and Ile-575 may also help secure the incoming peptide substrate to the open form of the enzyme. Arg-618 and Asp-145 are responsible for anchoring the invariant proline residue in the active site of this postproline-cleaving enzyme. A model is proposed for the docking of a representative substrate PQPQLPYPQPQLP in the active site, where the N-terminal substrate residues interact extensively with the catalytic domain, and the C-terminal residues stretch into the propeller domain. Given the promise of the M. xanthus PEP as an oral therapeutic enzyme for treating celiac sprue, our results provide a strong foundation for further optimization of the PEP's clinically useful features.
Title: Prolyl endopeptidase from Sphingomonas capsulata: isolation and characterization of the enzyme and nucleotide sequence of the gene Kabashima T, Fujii M, Meng Y, Ito K, Yoshimoto T Ref: Archives of Biochemistry & Biophysics, 358:141, 1998 : PubMed
Prolyl endopeptidase (prolyl oligopeptidase, EC 3.4.21.26) was purified from Sphingomonas capsulata IFO 12533, and its gene was cloned and expressed in Escherichia coli. The recombinant enzyme was markedly inhibited by diisopropyl phosphofluoridate and hardly affected by SH reagents or metal chelators, similar to the native enzyme purified from S. capsulata. Nucleotide sequencing analysis revealed an open reading frame of 2169 bp, coding for a protein of 723 amino acids with a predicted molecular weight of 78,433. The amino acid sequence was 39.6, 45.3, 38.9, and 38.3% homologous to Flavobacterium meningosepticum, Aeromonas hydrophila, porcine brain, and human T cell prolyl endopeptidase, respectively. A region near the C-terminus and the region containing the putative catalytic triad residues were highly conserved. The enzyme was crystallized by the hanging drop vapor diffusion method, using ammonium sulfate as a precipitant.
Sphingomonas capsulata (Flavobacterium capsulata)prolyl oligopeptidase precursor (EC 3.4.21.26) (PE)
